Whole blood is typically described as being made up of various cellular components such as red blood cells (RBCs), white blood cells (WBCs) and platelets, suspended in a liquid component, plasma. Each component plays a specific and important role in the human body. For example, platelets (together with clotting factors and other substances in the blood) are responsible for stopping bleeding. WBCs are primarily responsible for fighting disease. RBCs transport oxygen (O.sub.2) and carbon dioxide (CO.sub.2) to and from body tissues. The O.sub.2 and CO.sub.2 are carried by a protein called hemoglobin, which is found inside the RBC.
Whole blood can be (and is routinely) separated by centrifugation, membrane filtration or other techniques into its constituent components, and the separated component may be administered to a patient in need of that particular component. For example, RBCS may be administered to patients who have experienced rapid blood loss or to improve the oxygen carrying capability of blood in patients suffering from anemia and the like.
Most commonly, RBCs are separated from whole blood by introducing anticoagulated whole blood into a rotating centrifuge chamber. More specifically, whole blood is withdrawn from a donor through a needle that is inserted into the vein of the donor. The needle communicates with plastic tubing through which the blood flows to a (usually preattached) plastic container. The blood inside the plastic container is then subjected to a centrifugal force by rotating the centrifuge. Rotation of the centrifuge causes the components of whole blood to sediment into layers or bands based on the different densities of the components. The more dense (or "heavier") components, such as RBCs, are thus "separated" from the lighter components, such as platelets and plasma. The separated layer or band of RBCs may then be transferred to a separate (usually plastic) container where they are stored until transfusion to a patient. Alternatively, the plasma and platelets may be expressed from the collection container, leaving the RBCs in the collection container for storage.
For a variety of reasons, the storage period can last several days and sometimes even several weeks. Unfortunately, extended storage of RBCs may negatively affect the function and viability of RBCS. For example, one concern during the storage of RBCs is that the membrane surrounding the RBC cell will rupture. The rupturing of the RBC membrane is commonly referred to as "hemolysis". The hemolysis of RBCs results in the release of hemoglobin, thus, impairing the RBC's ability to transport O.sub.2 and CO.sub.2. These RBCs are less suitable for transfusion to a patient.
The plastic containers used for the storage of blood and/or blood cells must be made of materials that are, of course, suitable for the storage of blood and, preferably, enhance the viability of the stored blood cells. Some plastics, that may be otherwise suitable for storing blood and/or blood cells, may be too rigid for use in medical containers. Accordingly, these materials require a plasticizer to soften the material and provide the container with flexibility. One such material that has been commonly used for medical containers is polyvinyl chloride (PVC). Because PVC alone is too rigid to be used for flexible blood containers, it is typically combined with a plasticizer.
Several different plasticizers are suitable for use with PVC. For example, plasticizers from the family of phthalate esters, and in particular, di-2-ethylhexylphthalate (DEHP) have been used in combination with PVC resins. In addition to DEHP, plasticizers such as triethylhexyltrimellitate (TEHTM) have also been used with PVC resins. More recently, it has been discovered that citrate esters are capable of plasticizing PVC. PVC plasticized with citrate ester is described, for example, in U.S. Pat. Nos. 4,710,532, 4,789,700, 4,870,204, 4,883,905, 4,892,967, 4,931,583, 4,824,893, 4,711,922 and 4,954,649, all of which are incorporated by reference herein.
It has been observed that some plasticizers appear to have a beneficial effect on the viability of stored blood and/or red blood cells. More specifically, it has been observed that red blood cells stored in plastic containers that include certain plasticizers experience a lower rate of hemolysis than in containers free of plasticizers. It is believed that the interaction of the stored blood cells and the plasticizer (in the container wall) helps maintain the integrity of the RBC membrane, thus resulting in reduced hemolysis. Thus, even for those materials that are not as rigid as PVC and are otherwise suitable for use in the storage of blood, it may be beneficial that the plastic container include a sufficient amount of plasticizer to reduce the rate of hemolysis in the stored blood.
Examples of such blood storage containers are described in U.S. Pat. Nos. 5,026,347, 5,100,401 and 5,167,657, all of which are assigned to the assignee of the present of application and are incorporated by reference herein. The blood storage containers described therein are made from a plastic composition that includes polyolefin and citrate ester plastisizers. The polyolefin described in these patents, is a polyolefin copolymer that includes a central block of ethylene and butylene units with terminal blocks of styrene. The polyolefin is combined with a citrate ester plasticizer to form a plastic composition that is suitable for use in a blood storage container and wherein the amount of citrate ester is sufficient to suppress the level of hemolysis in stored red blood cells. The plastic material described therein may further include an amount of propylene.
Although the above described containers are believed to have worked satisfactorily, it has been observed that some polyolefins, when combined with plasticizers, appear to lose some of their flexibility and become more brittle after being subjected to high temperature heating (such as occurs during steam sterilization). It is believed that at least part of the reason for the material becoming more brittle after sterilization may be that high temperature heating results in a molecular rearrangement of the material, which increases the crystallinity (and, therefore, rigidity) of the material. However, in addition, it is believed that the decrease in flexibility results from the inability of the plastic material to retain the plasticizer within the body of the plastic material. Stated differently, it is believed that during heating, the plasticizer migrates out from the plastic material to the outer surface of the material. The migration of the plasticizer, therefore, results in there being less plasticizer available for contact with the stored blood cells. Ultimately, this may lead to reduced hemolysis suppression in the stored red blood cells. For these reasons, it is desirable to provide a plastic composition that can be used as a medical container, such as a container for storing blood and/or red blood cells, which remains flexible after being exposed to heat and/or retains most of the plasticizer during heating, such as in a steam sterilization process.